Group 3 Pulmonary Hypertension: Clinical Examples
Group 3 pulmonary hypertension encompasses PH due to chronic lung diseases and/or hypoxemia, with the most common examples being chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). 1
Primary Clinical Conditions
Obstructive Lung Diseases
- Chronic obstructive pulmonary disease (COPD) is the most frequently encountered cause of Group 3 PH, though severe PH (mean PAP ≥35 mmHg) is uncommon in this population 1, 2
- Combined emphysema/fibrosis syndrome demonstrates a particularly high prevalence of PH compared to isolated COPD 1
Interstitial and Restrictive Lung Diseases
- Interstitial lung disease (ILD) commonly develops mild PH, with severe PH occurring in a small proportion of patients 1, 2
- Other pulmonary diseases with mixed restrictive and obstructive patterns are included in this category 1
Sleep and Ventilation Disorders
- Sleep-disordered breathing represents a distinct subgroup where nocturnal hypoxemia drives pulmonary vascular changes 1
- Alveolar hypoventilation disorders cause PH through chronic hypoxemia and hypercapnia 1
Environmental and Developmental Causes
- Chronic exposure to high altitude produces PH through sustained hypoxic pulmonary vasoconstriction 1
- Developmental lung abnormalities can predispose to PH from early life 1
Hemodynamic Characteristics
Group 3 PH is defined by pre-capillary hemodynamics with mean PAP ≥25 mmHg (older guidelines) or >20 mmHg (newer definitions), pulmonary arterial wedge pressure ≤15 mmHg, and the presence of underlying lung disease 1
A critical distinction exists for severe Group 3 PH, defined as pulmonary vascular resistance >5 Wood units, which represents a pulmonary vascular phenotype with disproportionately severe vascular disease relative to the degree of lung parenchymal destruction 3
Clinical Pitfalls
Distinguishing symptoms of underlying lung disease from concomitant PH can be extremely difficult, as dyspnea and exercise limitation are common to both conditions 3. The presence of PH should be suspected when symptoms appear disproportionate to the severity of lung function impairment 2, 4.
Specific PAH-targeted therapies are not approved for Group 3 PH and may be harmful by worsening ventilation-perfusion mismatch and gas exchange 2. Treatment should focus on optimizing the underlying lung disease, supplemental oxygen to maintain saturation >90%, and pulmonary rehabilitation 2, 3.
The pulmonary vascular phenotype (severe PH with PVR >5 WU but relatively preserved lung function) may represent a distinct entity where PAH-specific therapies are being investigated, though this remains controversial and should only be considered in specialized centers 3.